Positron-emitting 68Ga (T1/2=68 min) is of potential interest for clinical positron emission tomography (PET). It is a generator produced radionuclide, does not require cyclotron on site and thus easily available and relatively cheap. 68Ga is a suitable radiometal for PET radiopharmaceutical production. However, such obstacles as the chemical form of 68Ga after generator elution, the large elution volume and the contamination of other cations originating from the column material and 68Ge breakthrough may have limited its use. Methods to surmount some of these drawbacks have been developed1,2 and might promote the wider use of 68Ga-based radiopharmaceuticals. Macrocyclic bifunctional chelators can form stable complexes with radiometal cations and covalently bind to macromolecules. The fact that the same chelator can complex different cations makes it possible to use the same biologically active molecule for diagnosis and therapy, employing corresponding radiometals. 68Ga has the potential for diagnosis, dosimetry, dose planning for chemo- and radiotherapy and follow up of response to chemo- and radiotherapy. These applications might require accurate quantification which is dependent on the specific radioactivity (SRA) of a tracer. This is especially important for the characterisation of high affinity binding sites, such as many peptide receptors. Another factor that necessitates the high SRA is the labelling of highly potent receptor agonists which can induce side effects. Cost of high molecular weight ligands might also be a factor to consider. A fast and reliable method for 68Ga-labelling of various macromolecules with high SRA has been developed. 1-3 However, we showed later that the achievement of SRA values comparable to the receptor concentration was most probably hindered by the presents of Fe(III). The latter is a strong competitor to 68Ga(III) in the complexation reaction with a chelator coupled to a peptide. The chemistry of Fe(III) and 68Ga(III) is very similar. Iron is an abundant cation and can be found in glassware, cartridges and chemicals. The removal of Fe(III) may improve the SRA and also omit any uncertainty over its role in the 68Ga-labelling process. The purification method1,3 developed at Uppsala University/Uppsala Imanet AB does not eliminate Fe(III). The method might be further improved by, for example, introduction of Fe(III) reduction to Fe(II). The adsorption profile of [FeCI4]− is very similar to that of [68GaCl4]− from 0.1-6.0 M HCl. This makes it difficult to separate the two cations as the anion complex on the anion exchange resin. In contrast, Fe(II) is not adsorbed from 4.0 M HCI acid and would pass through the anion exchange resin without retention. The purification of the 68Ge/68Ga generator eluate from Fe(III) might even further improve the SRA of 68Ga-based tracers comprising macromolecular ligands as well as small organic molecules. Specially, it could have a significant impact when using peptide, oligonucleotide, PNA, LNA, antibody, glycoprotein, protein and other biological macromolecule based ligands. Thus it might become possible to produce highly potent macromolecular 68Ga-based radiopharmaceuticals with high specific radioactivity and use them in humans without risk for pharmachological side effects. Moreover, 68Ga-based radiopharmaceuticals with high specific radioactivity would allow accurate quantification of PET examinations. This in turn would provide accurate in vivo quantification of receptor density for dosimetry, planning and follow up of chemo- and radiotherapy.
There is therefore a need in the art for a more effective and efficient method for purifying 68Ge/68Ga generator produced 68Ga from Fe (III).